Aging alters the individual's physiological and functional responses to external stimuli, including the responses to infectious agents and therapeutics including biological response modifiers. We therefore examined the effect of aging on immunity. As a model, we utilized the cytolytic T lymphocyte (CTL) response generated against alloantigens. Although we have observed a reduction in the number of alloantigen- stimulating cells producing perforin or pore-forming protein (Pfp) with age, the reduction was small compared to the reduced cytolytic activity. We found that the Pfp level was reduced on a per cell basis, suggesting that (1) a threshold level of Pfp may be required for potency of effector cell function, and (2) aging may affect most or all potential effector cells rather than a "mosaic" of cells. We have examined allogeneic CTL generated in response to antigens stimulating either CD4-positive or CD8-positive T helper and T effector cell function. We found that age-related effect was most evident in the CD4-positive T cell-dependent system in vitro and in vivo. . We have observed that the decline in CD4-positive cell activity correlates with an alteration in expression of T cell receptors. Current efforts are focused on defining the difference in T cell antigen receptor expression in CD4-positive cells from young and aged mice.